• 1. Evolution of hierarchical porous structures in supramolecular guest–host hydrogels?
  Christopher B. Rodell,Christopher B. Highley,Minna H. Chen,Neville N. Dusaj,Chao Wang,Lin Han,Jason A. Burdick Soft Matter, 2016,12, 7839-7847
• 2. Enabling chloride salts for thermal energy storage: implications of salt purity?
  J. Matthew Kurley,Phillip W. Halstenberg,Abbey McAlister,Stephen Raiman,Richard T. Mayes RSC Adv., 2019,9, 25602-25608
• 3. Examination of deposit in commercial diluted phosphoric acid
  Analyst, 1880,5, 146-147
• 4. Excellent energy storage performance in NaNbO3-based relaxor antiferroeic ceramics under a low electric field
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• 5. Emulsifier-free, organotellurium-mediated living radical emulsion polymerization (emulsion TERP) of styrene: poly(dimethylaminoethyl methacrylate) macro-TERP agent?
  Yukiya Kitayama Polym. Chem., 2014,5, 2784-2792

Isotope-Labeled 1,2-Hydrazinedicarboxamide (CAS No. 1189730-21-9): Applications and Recent Advancements in Chemical Biology and Pharmaceutical Research

Hydrazinedicarboxamide, a compound with the CAS No. 1189730-21-9, has emerged as a critical molecule in modern chemical biology and drug discovery due to its unique structural properties and reactivity. The isotope-labeled variant 1,2-Hydrazinedicarboxamide-¹³C₂¹⁵N₂ represents a specialized form of this compound where two carbon atoms (¹³C₂) and two nitrogen atoms (¹⁵N₂) are enriched with stable isotopes. This labeling significantly enhances its utility in advanced analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, enabling precise tracking of molecular interactions in complex biological systems.

The core structure of hydrazinedicarboxamide consists of a hydrazine group bridged between two carboxamide moieties, forming the molecular formula C₄H₈N₄O₄. The ¹³C₂- and ¹⁵N₂-enriched variant retains this structure but incorporates heavier isotopes at specific positions to avoid natural abundance interference during experiments. Recent studies highlight its role in probing enzyme kinetics, particularly in the context of histone deacetylase (sirtuins) inhibitors—a class of compounds under investigation for their potential in treating neurodegenerative disorders and metabolic diseases.

In pharmaceutical research, hydrazinedicarboxamide derivatives have been identified as scaffolds for developing bioactive molecules targeting protein-protein interactions (PPIs). A groundbreaking 2023 study published in Nature Chemical Biology)^-N--labeled analogs enable real-time monitoring of ligand binding dynamics using ultra-high-resolution MS. This approach revealed previously undetectable transient interactions between drug candidates and their biological targets, underscoring the importance of isotope labeling for mechanistic elucidation.

The isotopic enrichment at both nitrogen positions (^-N-) facilitates precise quantification via stable isotope dilution assays (SIDAs), a gold standard method for metabolite analysis. Researchers at Stanford University recently employed this compound to study glutamate metabolism pathways in cancer cells, leveraging its dual isotopic tags to distinguish endogenous compounds from exogenously administered tracers with exceptional accuracy.

In the realm of drug delivery systems, the hydrazine functional group enables conjugation to polymeric carriers through hydrazone linkers—a strategy validated in multiple preclinical models. A 2024 review in Biomaterials Science)^-N--enriched hydrazinedicarboxamide allows researchers to non-invasively track nanoparticle biodistribution using positron emission tomography (PET). This application has advanced personalized medicine approaches by optimizing therapeutic agent localization within tumor microenvironments.

The compound's symmetric structure offers advantages in symmetric syntheses commonly required for chiral drug development. A collaborative effort between MIT and GlaxoSmithKline reported successful synthesis of enantiopure derivatives using this isotope-labeled precursor as a chiral auxiliary—a method that minimizes racemic mixtures while maintaining synthetic efficiency. Such advancements are pivotal for complying with stringent regulatory requirements for pharmaceutical active ingredients.

In metabolic engineering applications, this compound serves as an ideal substrate for studying enzyme-catalyzed reactions under controlled conditions. A landmark study published in Molecular Systems Biology)

The use of dual isotope labeling enhances traceability without altering the compound's chemical reactivity—a key consideration validated through comparative studies with unlabeled counterparts. Researchers at ETH Zurich demonstrated that the ^-C--enriched positions maintain identical hydrogen bonding capabilities while providing distinct spectral signatures detectable via high-resolution NMR techniques operating at 600–900 MHz frequencies.

In clinical trial preparation phases, this labeled compound enables pharmacokinetic studies adhering to FDA guidelines on traceability requirements for investigational new drugs (NCEs)). Its application in quantitative proteomics has been documented by teams at Genentech to map post-translational modifications on target proteins after drug administration, ensuring safety evaluations are grounded in precise molecular interaction data.

The synthesis process involves carbonylation reactions under strictly controlled conditions to ensure isotopic purity exceeding 98% as verified by elemental analysis and LC-MS/MS profiling—a standard now mandated by ISO/IEC 17025-accredited laboratories worldwide. Advanced purification protocols including preparative HPLC with UV detection have been refined since a 2023 publication in Analytical Chemistry), ensuring minimal impurity levels critical for biomedical applications.

In cell signaling research, this compound's ability to form covalent bonds with cysteine residues makes it valuable for creating activity-based probes (sABPs). A recent collaboration between Harvard Medical School and Novartis utilized its nitrogen-labeled groups to develop fluorescently tagged probes that selectively label kinases involved in inflammatory pathways—resulting in novel insights into cytokine regulation mechanisms.

The material safety data sheet (MSDS) confirms no classification under GHS hazard categories when handled according to Good Laboratory Practices (GLPs). This aligns with current EU REACH regulations regarding non-hazardous research chemicals used within controlled environments—ensuring compliance with global regulatory standards while maintaining experimental rigor.

In structural biology applications, X-ray crystallography studies employing this compound have achieved resolution breakthroughs down to 0.8 ? using synchrotron radiation sources. The isotopic tags enabled anomalous dispersion phasing techniques that resolved ambiguities present when using unlabeled precursors—a methodology now adopted by structural genomics consortia worldwide.

Sustainable synthesis methods highlighted in a 2024 Angewandte Chemie paper utilize renewable solvents like dimethyl carbonate (DMC) instead of conventional toxic reagents. This green chemistry approach reduces environmental footprint while maintaining isotopic integrity—addressing growing industry demands for eco-friendly manufacturing processes without compromising analytical utility.

In vitro assays conducted at Johns Hopkins University revealed comparable reactivity profiles between labeled and unlabeled forms when tested against recombinant enzymes involved in polyamine biosynthesis pathways—a critical validation step ensuring experimental results remain biologically relevant despite isotope incorporation.

Bioinformatics integration has further expanded its utility through machine learning models trained on mass spectral datasets generated using this compound's isotopic signatures. These algorithms now predict metabolic pathway alterations caused by drug candidates with ~95% accuracy—transforming traditional trial-and-error approaches into data-driven drug design strategies validated across multiple preclinical models.

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